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Semin Hematol. 1999 Jan;36(1):3-18.

The wide spectrum and unresolved issues of megaloblastic anemia.

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1
Imperial College of Science, Technology and Medicine, University of London, UK.

Abstract

Several fundamental questions relating to the biochemical basis of megaloblastic hemopoiesis in vitamin B12 (B12) and folate deficiency and neurological damage in B12 deficiency remain to be answered. Among them is the explanation underlying (1) the failure of B12-deficient animals to develop megaloblastic hemopoiesis despite indirect evidence of impaired thymidylate synthesis and (2) the inverse relationship between the extent of hematologic and neurological damage in B12 deficiency. Diagnostic advances have led to the awareness that many patients with B12 or folate deficiency are hematologically normal and that subtle hematologic or neuropsychiatric manifestations may be found at a fairly early stage of developing B12 deficiency. Studies of the mechanism of absorption of B12 in food have identified the syndrome of food B12 malabsorption in which the degree of B12 deficiency is commonly, although not invariably, mild. Folate intake influences the prevalence of neural tube defects (NTDs) and a suboptimal folate status may be associated with an increased risk for dysplasia and cancer. The latter may be at least partly the result of uracil misincorporation into DNA and consequent DNA strand breaks. Folate status has also been linked to arteriosclerotic vascular disease through its effect on serum homocysteine levels. Uracil misincorporation into DNA and increased serum homocysteine levels may also be found in B12 deficiency. These adverse associations form the basis of a case for improving B12 or folate status in individuals with a mild degree of deficiency. Because inadequate folate intake is relatively common, especially in the elderly and the poor, the fortification of staple foods with folate is currently under active consideration.

PMID:
9930565
[Indexed for MEDLINE]

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